rs45511401

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3BP4_StrongBA1

The NM_004996.4(ABCC1):c.2012G>T(p.Gly671Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,613,958 control chromosomes in the GnomAD database, including 1,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.036 ( 131 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1826 hom. )

Consequence

ABCC1
NM_004996.4 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 8.01

Publications

82 publications found

Variant links:

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra-and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

ABCC1 Gene-Disease associations (from GenCC):

hearing loss, autosomal dominant 77
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0040707886).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4 link	c.2012G>T	p.Gly671Val	missense_variant	Exon 16 of 31	ENST00000399410.8	NP_004987.2	P33527-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8 link	c.2012G>T	p.Gly671Val	missense_variant	Exon 16 of 31	1	NM_004996.4	ENSP00000382342.3		P33527-1

Frequencies

GnomAD3 genomes

AF:

0.0358

AC:

5449

AN:

152128

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0505

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0536

Gnomad OTH

AF:

0.0330

GnomAD2 exomes

AF:

0.0380

AC:

9480

AN:

249312

AF XY:

0.0388

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0323

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.0604

Gnomad NFE exome

AF:

0.0562

Gnomad OTH exome

AF:

0.0394

GnomAD4 exome

AF:

0.0477

AC:

69742

AN:

1461712

Hom.:

1826

Cov.:

AF XY:

0.0471

AC XY:

34222

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.00875

AC:

293

AN:

33478

American (AMR)

AF:

0.0181

AC:

808

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

911

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0168

AC:

1446

AN:

86246

European-Finnish (FIN)

AF:

0.0604

AC:

3226

AN:

53396

Middle Eastern (MID)

AF:

0.0295

AC:

170

AN:

5766

European-Non Finnish (NFE)

AF:

0.0542

AC:

60274

AN:

1111890

Other (OTH)

AF:

0.0432

AC:

2611

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

3812

7623

11435

15246

19058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2154

4308

6462

8616

10770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0358

AC:

5446

AN:

152246

Hom.:

131

Cov.:

AF XY:

0.0343

AC XY:

2553

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0120

AC:

497

AN:

41562

American (AMR)

AF:

0.0299

AC:

458

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0383

AC:

133

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.0122

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0505

AC:

535

AN:

10602

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0536

AC:

3643

AN:

68004

Other (OTH)

AF:

0.0331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

261

522

784

1045

1306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0469

Hom.:

691

Bravo

AF:

0.0337

TwinsUK

AF:

0.0553

AC:

205

ALSPAC

AF:

0.0529

AC:

204

ESP6500AA

AF:

0.0119

AC:

ESP6500EA

AF:

0.0559

AC:

473

ExAC

AF:

0.0392

AC:

4744

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0546

EpiControl

AF:

0.0544

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Atorvastatin response

Other:1

Apr 13, 2022

Pharmacometrics, Pharmacogenomics, Pharmacokinetics Research Group, Catholic University of Louvain

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:in vitro

functional variant -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

D;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D

MetaRNN

Benign

0.0041

T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Pathogenic

4.5

H;.

PhyloP100

8.0

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-7.8

D;.

REVEL

Pathogenic

0.78

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.71

MPC

1.2

ClinPred

0.10

GERP RS

4.8

Varity_R

0.98

gMVP

0.97

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over